POS0070 CONTINUED TREATMENT WITH NINTEDANIB IN PATIENTS WITH LIMITED CUTANEOUS SYSTEMIC SCLEROSIS (lcSSc) AND INTERSTITIAL LUNG DISEASE (ILD)
Authors: Y. Allanore, D. Khanna, V. Smith, M. Aringer, A. M. Hoffmann-Vold, M. Kuwana, P. A. Merkel, A. James, S. Sambevski, M. Alves, C. P. Denton
Journal: Annals of the Rheumatic Diseases (2022)

Background Few data are available on the progression and management of ILD, or the management of adverse events associated with drug treatment, in patients with lcSSc. SENSCIS-ON is an open-label extension trial that is collecting data on decline in forced vital capacity (FVC) and adverse events in patients treated with nintedanib over the long term. Objectives To assess decline in FVC and adverse events in patients with lcSSc and ILD treated with nintedanib in SENSCIS-ON. Methods Patients with SSc-ILD were eligible to enter SENSCIS-ON if they completed the randomized placebo-controlled SENSCIS trial (in which patients received trial drug until the last patient reached week 52 but for ≤100 weeks) or a drug–drug interaction (DDI) study of nintedanib and oral contraceptive (in which female patients received nintedanib for ≤28 days). Among patients with lcSSc, we analysed changes from baseline in FVC and adverse events over 52 weeks of SENSCIS-ON in patients who received nintedanib in SENSCIS and continued it in SENSCIS-ON (“continued nintedanib” group) and in patients who received placebo in SENSCIS and initiated nintedanib in SENSCIS-ON or who received nintedanib for a short time in the DDI study (“initiated nintedanib” group). Analyses were descriptive. Results There were 98 patients with lcSSc in the continued nintedanib group and 127 patients with lcSSc (114 from SENSCIS, 13 from the DDI study) in the initiated nintedanib group. In these groups, respectively, mean (SD) FVC values at inclusion in SENSCIS-ON were 2449 (662) mL and 72.7(16.7) % predicted and 2508 (771) mL and 74.1 (17.4) % predicted. Mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were −45.1 (19.1) mL in the continued nintedanib group, −41.5 (24.0) mL in the initiated nintedanib group, and −43.3 (15.3) mL in all patients with lcSSc, similar to the change in FVC in patients with lcSSc at week 52 of the SENSCIS trial (−39.1 [22.2] mL). The adverse event profile of nintedanib in SENSCIS-ON was consistent with that reported over 52 weeks of the SENSCIS trial (Table 1). Over 52 weeks, adverse events led to discontinuation of nintedanib in 3.1% of patients with lcSSc who continued nintedanib in SENSCIS-ON and 16.5% who initiated nintedanib in SENSCIS-ON. Table 1. Adverse events (irrespective of causality) reported over 52 weeks in patients with lcSSc and ILD in SENSCIS and SENSCIS-ON. SENSCIS SENSCIS-ON Nintedanib(n=135) Placebo(n=142) Continued nintedanib(n=98) Initiated nintedanib(n=127) Most frequent adverse events* Diarrhoea 104 (77.0) 43 (30.3) 70 (71.4) 89 (70.1) Nausea 45 (33.3) 20 (14.1) 19 (19.4) 32 (25.2) Vomiting 33 (24.4) 16 (11.3) 15 (15.3) 31 (24.4) Nasopharyngitis 21 (15.6) 29 (20.4) 18 (18.4) 23 (18.1) Upper respiratory tract infection 18 (13.3) 19 (13.4) 13 (13.3) 18 (14.2) Skin ulcer 11 (8.1) 18 (12.7) 11 (11.2) 14 (11.0) Cough 17 (12.6) 25 (17.6) 13 (13.3) 8 (6.3) Adverse event(s) leading to permanent treatment discontinuation 25 (18.5) 12 (8.5) 3 (3.1) 21 (16.5) Adverse event(s) leading to dose reduction 47 (34.8) 5 (3.5) 17 (17.3) 62 (48.8) Serious adverse event(s) 30 (22.2) 26 (18.3) 22 (22.4) 31 (24.4) n (%) of patients with lcSSc with ≥1 such event reported over 52 weeks (or until 28 days after last drug intake if earlier in SENSCIS or until 7 days after last trial drug intake if earlier in SENSCIS-ON). *Adverse events reported in &gt;10% of patients with lcSSc in either group in SENSCIS-ON. Adverse events were coded according to preferred terms in the Medical Dictionary for Regulatory Activities. Conclusion The change in FVC in patients with lcSSc and ILD who received nintedanib over 52 weeks, and the safety profile of nintedanib, in SENSCIS-ON were similar to that observed in patients with lcSSc and ILD who received nintedanib in SENSCIS. These analyses support a continued effect of nintedanib on slowing decline in FVC and the ability to manage adverse events of nintedanib in patients with lcSSc and ILD over the longer term. Acknowledgements The SENSCIS-ON trial was funded by Boehringer Ingelheim. Disclosure of Interests Yannick Allanore Consultant of: Abbvie, AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Medsenic, Mylan, Prometheus, Roche, Sanofi, Grant/research support from: Alpine Immunosciences, Medsenic, OSE immunotherapeutics, Dinesh Khanna Shareholder of: Stocks - Eicos Sciences, Inc., Consultant of: AbbVie, Acceleron, Actelion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, Genentech/Roche, Gilead, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp &amp; Dohme, Mitsubishi Tanabe Pharma, Prometheus, Sanofi-Aventis, Theraly, United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health, Pfizer, Employee of: Leadership/Equity position – Chief Medical Officer - CiviBioPharma/Eicos Sciences, Inc, Vanessa Smith Speakers bureau: Actelion Pharmaceuticals, Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV, UCB Biopharma Sprl , Consultant of: Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV , Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer-Ingelheim Pharma GmbH&amp;Co, Janssen-Cilag NV, Research Foundation - Flanders (FWO) , Martin Aringer Speakers bureau: AbbVie, AstraZeneca, Boehringer Ingelheim, BristolMyersSquibb, Chugai, Galapagos, GlaxoSmithKline, Lilly, MSD, Novartis, Otsuka, Pfizer, Roche, Sanofi, UCB , Consultant of: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Galapagos, GlaxoSmithKline, Lilly, Pfizer, Roche, Sanofi , Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Paid instructor for: Boehringer Ingelheim, Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp &amp; Dohme, Roche, Grant/research support from: Boehringer Ingelheim, Masataka Kuwana Speakers bureau: AbbVie, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai, Eisai, GlaxoSmithKline, Janssen, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi , Consultant of: AstraZeneca, Boehringer Ingelheim, Corbus, Mochida Kissei , Grant/research support from: Boehringer Ingelheim, MBL, Ono Pharmaceuticals , Peter A Merkel Consultant of: AbbVie, AstraZeneca, Boeringher Ingelheim, Bristol-Myers Squibb, ChemoCentryx, CSL Behring, Dynacure, EMDSerono, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, Immagene, InflaRx, Jannsen, Kiniksa, Kyverna, Magenta, MiroBio, Neutrolis, Novartis, Pfizer, Regeneron, Sparrow, Takeda, Talaris , Grant/research support from: AbbVie, AstraZeneca, Boeringher Ingelheim, Bristol-Myers Squibb, ChemoCentryx, Eicos, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Sanofi, Takeda , Alexandra James Employee of: Alexandra James is an employee of Elderbrook solutions GmbH that is contracted by Boehringer Ingelheim, Steven Sambevski Employee of: Steven Sambevski is an employee of Boehringer Ingelheim, Margarida Alves Employee of: Margarida Alves is an employee of Boehringer Ingelheim, Christopher P Denton Speakers bureau: Boehringer Ingelheim, Janssen, Consultant of: Abbvie, Acceleron, Boehringer Ingelheim, Corbus, CSL Behring, GlaxoSmithKline, Roche, Grant/research support from: ARXX Therapeutics, GlaxoSmithKline, Horizon Therapeutics, Servier